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1、HDL and Coronary Heart Disease,Angiographic and Clinical Event Trials,Angiographic Trials of Combination Therapy,Cholesterol Lowering Atherosclerosis Study (CLAS)1 Diet and niacin + colestipol (vs diet and placebo) 188 men (aged 4059 y), post-CABG Nonsmokers or former smokers, nondiabetic, nonhypert
2、ensive Total-C at entry: 185350 mg/dL; drug responsive Familial Atherosclerosis Treatment Study (FATS)2 Lovastatin + colestipol, niacin + colestipol, or conventional therapy 146 men (aged 62 y) with CAD and family history of CAD ApoB 125 mg/dL Average stenosis: 34%,1. Blackenhorn DH et al. JAMA. 198
3、7;257:32333240 2. Brown G et al. N Engl J Med. 1990;323:12891298,Angiographic Trials of Combination Therapy Effects on Lipids,% change Trial LDL-C HDL-C TG CLAS Placebo (2 y)1 5* 2 5* Niacin + colestipol (2 y)1 43* 37* 22* Niacin + colestipol (4 y)2 40 37 18 FATS (2.5 y)3 Conventional 7* 6* 15 Niaci
4、n + colestipol 32* 41* 29* Lovastatin + colestipol 45* 16 9,Versus baseline: *P 0.001; P 0.01; * P 0.05; Versus placebo: P 0.001; P 0.03 1. Blankenhorn DH et al. JAMA 1987;257:32333240 2. Cashin-Hemphill L et al. JAMA 1990;264:30133017 3. Brown BG et al. N Engl J Med 1990;323:12891298,Cholesterol-Lo
5、wering Atherosclerosis Study (CLAS) Univariate Apo Predictors of Coronary Progression,Mean (mg/dL) Predictor Progressor Nonprogressor P value Placebo (n = 82: 49 progressors, 33 nonprogressors) ApoB 128 116 0.03 ApoC-III (total) 12.4 10.3 0.03 ApoC-III (HS)* 5.9 4.9 0.03 Drug (n = 80: 31 progressors
6、, 49 nonprogressors) ApoC-III (HS)* 6.4 7.5 0.05,*HS = heparin supernate (apoC-III in HDL) Blankenhorn DH et al. Circulation 1990;81:470476,Familial Atherosclerosis Treatment Study (FATS) Univariate Predictors of Change in Proximal Stenosis,Predictor r P value ApoB 0.38 0.0001 LDL-C 0.27 0.01 HDL-C
7、-0.33 0.001 ApoA-I -0.28 Not reported,Brown G et al. N Engl J Med 1990;323:12891298,Angiographic Trials of Fibrate Therapy,Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT)1 Bezafibrate vs placebo 92 male survivors of MI, aged 45 y at time of event Coronary angiography at baseline and
8、 after 2 and 5 y Lopid Coronary Angiography Trial (LOCAT)2 Gemfibrozil vs placebo 395 men, post-CABG Coronary angiography at baseline and after 32 mos,1. Ericsson CG et al. Lancet 1996;347:849853 2. Frick MH et al. Circulation 1997;96:21372143,Bezafibrate Coronary Atherosclerosis Intervention Trial
9、(BECAIT) Effect on Lipid Levels at 5 Years,Change from baseline: *P 0.001; P = 0.551; *P = 0.020 Bez = bezafibrate 200 mg TID (n = 42); Plac = placebo (n = 39) Ericsson CG et al. Lancet 1996;347:849853,-14.0*,-3.5,8.6*,-26.3*,-5.6,-2.2,-0.8,2.7,-30,-25,-20,-15,-10,-5,0,5,10,Total-C,LDL-C,HDL-C,Total
10、-TG,Bez Plac (266) (267),Median baseline (mg/dL):,Bez Plac (180) (179),Bez Plac (34) (39),Bez Plac (216) (175),Median % change from baseline,15,-35,Lopid Coronary Angiography Trial (LOCAT) Effect on Lipid Levels at 1 Year,*P 0.001 for between-group difference and for change from baseline Frick MH et
11、 al. Circulation 1997;96:21372143,-5.5*,-4.5*,21*,-36*,5.1,5.3,7.0,4.6,-40,-30,-20,-10,0,10,20,30,Total-C,LDL-C,HDL-C,TG,Gemfibrozil Placebo,Mean % change from baseline,Angiographic Trial of Statin Therapy,Lipoprotein and Coronary Atherosclerosis Study (LCAS) Fluvastatin versus placebo in patients w
12、ith low versus higher HDL-C Angiographic data from 339 patients: 68 with baseline HDL-C 35 mg/dL 271 with baseline HDL-C 35 mg/dL,Ballantyne CM et al. Circulation 1999;99:736743,Lipoprotein and Coronary Atherosclerosis Study (LCAS) Benefit of Statin Therapy in Patients With Low HDL-C,0.30,0.25,0.20,
13、0.15,0.10,0.05,0,HDL-C 35 mg/dL,HDL-C 35 mg/dL,Fluvastatin Placebo,Decrease in minimum lumen diameter (mm),P = 0.09,P = 0.0004,P for interaction = 0.01,Ballantyne CM et al. Circulation 1999;99:736743,-0.065,-0.274,-0.036,-0.083,Lipoprotein and Coronary Atherosclerosis Study (LCAS) Event-Free Surviva
14、l,2.5,1.00,0.75,0.50,0.25,0.00,0,1,2,Probability of event-free survival,1.00,0.75,0.50,0.25,0.00,0,1,2,2.5,Probability of event-free survival,Fluvastatin,Fluvastatin,Placebo,Placebo,HDL-C 35 mg/dL,HDL-C 35 mg/dL,P = 0.002,P = 0.232,Time (y),Time (y),Ballantyne CM et al. Circulation 1999;99:736743,An
15、giographic Trials in Patients With Low HDL-C Effects on Lipids,Trial (pts with Agent Baseline (mg/dL) % change evaluable angiography) (dosage) LDL-C HDL-C LDL-C HDL-C BECAIT (N = 81) Bezafibrate 180 34 3.5 9 (600 mg/d) LOCAT (N = 372) Gemfibrozil 138 31 4.5 21 (1,200 mg/d) LCAS (N = 339) Fluvastatin 146 43 25 9 (40 mg/d) LCAS (HDL-C Fluvastatin 143 32 25 16 35 mg/dL) (40 mg/d) (N = 68),Ballantyne CM et al. Circulation 1999;99:736743,Helsinki Heart Study,Primary-prevention, placebo-controlled trial to determine whether increasing HDL-C levels and decreasing LDL-C levels would red
